It is proposed to develop a model in the rat for the biochemical study of the induction and growth characteristics of trophoblastic neoplasia. It has been demonstrated that dimethylbenzanthracene will induce trophoblastic neoplasia in fetectomized rats, that the success rate of tumor induction may be enhanced by the presence of altered ratios or levels of estrogen and progesterone metastases have been reported to occur, and these tumors secrete unique proteins which can be used as markers to follow tumor induction and growth. A sensitive radioimmunoassay will be developed to detect and quantitate these proteins. The growth and development of induced tumors will be studied by quantitating the secretory protein(s), by histologic examination of rats sacrificed at specified time intervals post-tumor induction and by measuring key glycolytic, tricarboxylic acid cycle and pentose phosphate enzymes in both tumor tissue and endometrium, in relation to both time after tumor induction and estrogen and/or progesterone treatment. It is important to emphasize that trophoblastic neoplasia is a disease confined almost exclusively to humans. Consequently, little is known of the induction and early development of the disease because of the severe limitations imposed on studies by the nature of the host. Primary areas of biochemical study have been done in aborted or evacuated molar tissue and in cell culture lines. Cell culture lines are studied extensively, but even the ability to study their growth in immunosuppressed animals represents a model far removed from the type of environment in which trophoblastic neoplasia occurs. There remains an urgent need for a model in which trophoblastic neoplasia can be induced in vivo and followed throughout its growth and development. The proposed model may represent an improvement in these respects.